What should a general neurologist know about neuro‑ophthalmology, including key clinical presentations, examination techniques, red‑flag signs, initial work‑up, and first‑line management of common neuro‑ophthalmic disorders?

Essential Neuro-Ophthalmology Knowledge for General Neurologists

As a general neurologist, you must recognize that neuro-ophthalmic emergencies represent both vision-threatening and life-threatening conditions requiring immediate diagnosis and treatment, with many conditions carrying high stroke risk (up to 25%) or permanent vision loss if not managed within hours. 1

Critical Red-Flag Presentations Requiring Immediate Action

Giant Cell Arteritis (GCA) - The Most Urgent Emergency

• Any patient over 50 with new vision loss, headache, jaw claudication, scalp tenderness, or temporal artery tenderness requires immediate ESR/CRP testing and empiric high-dose corticosteroids before confirming the diagnosis. 1, 2, 3
• Delay in treatment risks bilateral blindness and stroke. 1
• Start prednisone 1 mg/kg (60-80 mg daily) immediately if GCA is suspected, even before temporal artery biopsy. 1

Acute Retinal Artery Occlusion - "Eye Stroke"

• Central retinal artery occlusion (CRAO) and branch retinal artery occlusion (BRAO) require emergency stroke center evaluation within hours, as 24-31% of patients have concurrent silent cerebral infarctions and up to 25% stroke risk. 1
• Order urgent brain MRI with diffusion-weighted imaging (DWI-MRI), which detects acute cerebral infarctions in 27-76% of CRAO patients and 11.8-30.8% of transient monocular vision loss patients. 1
• Even transient monocular vision loss (amaurosis fugax) requires urgent stroke workup—this is not a "benign" symptom. 1
• Immediate carotid imaging, echocardiography, and hypercoagulable workup are mandatory. 1

Papilledema and Increased Intracranial Pressure

• Papilledema on fundoscopy mandates urgent neuroimaging (MRI brain with contrast preferred) to exclude mass lesion, venous sinus thrombosis, or idiopathic intracranial hypertension. 2, 3
• Look for bilateral optic disc swelling, venous engorgement, and absence of spontaneous venous pulsations. 3
• Untreated papilledema causes permanent vision loss from optic atrophy. 2, 3

Essential Examination Skills You Must Master

Pupillary Examination

• Always check for relative afferent pupillary defect (RAPD) using the swinging flashlight test—this is the single most important sign of asymmetric optic nerve dysfunction. 2
• A dilated, poorly reactive pupil with third nerve palsy suggests aneurysmal compression requiring emergency vascular imaging. 1
• Horner syndrome (miosis, ptosis, anhidrosis) may indicate carotid dissection—a critical stroke risk. 1, 4

Fundoscopic Examination

• You must be able to identify: papilledema, optic disc pallor (atrophy), retinal emboli, "boxcarring" of retinal vessels, cotton-wool spots, and retinal hemorrhages. 1, 2, 3
• Optic disc pallor indicates chronic optic nerve damage and requires investigation for compressive, ischemic, inflammatory, or hereditary causes. 2

Visual Field Testing by Confrontation

• Bitemporal hemianopia localizes to the optic chiasm—immediately suspect pituitary adenoma, craniopharyngioma, or suprasellar meningioma requiring urgent MRI. 5
• Homonymous hemianopia indicates retrochiasmal pathology (stroke, tumor, demyelination). 5
• Central scotomas suggest optic nerve pathology. 2

Common Neuro-Ophthalmic Presentations and Initial Management

Acute Optic Neuritis

• Typical presentation: subacute painful monocular vision loss in young adults (20-40 years), worse with eye movement, with RAPD but often normal-appearing disc initially. 6
• Order brain MRI with contrast to assess multiple sclerosis (MS) risk—even one T2 hyperintense brain lesion dramatically increases MS likelihood. 5, 6
• Red flags for atypical optic neuritis requiring different workup: bilateral simultaneous involvement, painless presentation, posterior optic nerve/chiasm involvement, long lesions (>3 segments), or perioptic enhancement—these suggest neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody disease, sarcoidosis, or infection. 5, 6
• Consider IV methylprednisolone 1 gram daily for 3-5 days for severe vision loss or high MS risk. 6

Diplopia and Cranial Nerve Palsies

Third Nerve Palsy

• Pupil-involving third nerve palsy (dilated, poorly reactive pupil) is a neurosurgical emergency—assume posterior communicating artery aneurysm until proven otherwise with CT angiography or MR angiography. 1
• Pupil-sparing third nerve palsy in patients >50 with vascular risk factors suggests microvascular ischemia—observe for 3 months, but image if no improvement. 1
• Presentation: ptosis, eye abducted and infraducted, limited adduction/elevation/depression. 1

Sixth Nerve Palsy

• Most common cranial neuropathy causing horizontal diplopia worse at distance and in lateral gaze. 1
• In young patients or those with other neurologic signs, papilledema, or no vascular risk factors, obtain MRI brain with contrast to exclude mass, demyelination, or increased intracranial pressure. 1
• In older patients with diabetes/hypertension, observe for 6 months—if no improvement, image. 1

Skew Deviation

• Vertical misalignment from brainstem or vestibular pathology, often with head tilt and subjective visual vertical tilt. 1
• Distinguish from fourth nerve palsy using the upright-supine test (skew changes with position). 1
• Associated with stroke, demyelination, or vestibular neuronitis—requires neuroimaging and neurology/ENT referral. 1

Myasthenia Gravis - "The Great Masquerader"

• Suspect in any patient with variable, fatigable diplopia and/or ptosis that worsens throughout the day. 1
• Order acetylcholine receptor antibodies (positive in 40-77% of ocular myasthenia) and consider single-fiber EMG (positive in >90%). 1
• Ice pack test: apply ice to closed eyelid for 2 minutes—improvement in ptosis suggests myasthenia. 1
• Refer to neurology for pyridostigmine, corticosteroids, or immunosuppression; chest CT to exclude thymoma. 1

Mandatory Neuroimaging Protocols

When to Order MRI vs. CT

• MRI brain and orbits with and without gadolinium contrast is the gold standard for neuro-ophthalmic evaluation—superior for optic nerve pathology, chiasmal lesions, demyelination, and vascular abnormalities. 2, 3, 5, 7
• Use coronal fat-suppressed T2-weighted sequences for optic nerve visualization and post-contrast fat-suppressed T1 for enhancement. 5
• CT with contrast is acceptable only when MRI is contraindicated or unavailable, or when evaluating for bone erosion or calcification. 3, 5

Specific Imaging Indications

• All unexplained optic atrophy requires MRI brain and orbits with contrast to exclude compressive lesions, demyelination, or infiltrative disease. 2, 5
• Acute retinal artery occlusion requires DWI-MRI within 7 days to detect silent cerebral infarctions. 1
• New-onset headache with vision changes in patients >50 requires neuroimaging to exclude tumor, stroke, or subdural hematoma. 3

Essential Laboratory Testing

Age-Specific Screening

• All patients >50 with acute vision loss or new headache: ESR and CRP to exclude GCA. 1, 2, 3
• Acute retinal artery occlusion: complete stroke workup including lipid panel, hemoglobin A1c, hypercoagulable panel, antiphospholipid antibodies. 1
• Young patients with BRAO or stroke: consider Susac syndrome (hearing loss, CNS lesions, BRAOs) or carotid dissection. 1

Optic Neuritis Workup

• Brain MRI with contrast for MS risk stratification. 5, 6
• If atypical features: aquaporin-4 antibodies (NMOSD), MOG antibodies, ACE level (sarcoidosis), ANA, RPR/VDRL. 5, 6

Critical Management Principles

What You Can Initiate Immediately

• GCA suspected: start prednisone 60-80 mg daily immediately, do not wait for biopsy. 1
• Acute retinal artery occlusion: transfer to stroke center, consider ocular massage, anterior chamber paracentesis (if within 24 hours), hyperbaric oxygen (controversial). 1
• Acute angle-closure glaucoma: topical beta-blocker, alpha-agonist, carbonic anhydrase inhibitor, plus oral acetazolamide 500 mg, then urgent ophthalmology referral. 3

When to Refer Urgently to Ophthalmology

• Papilledema identified on fundoscopy. 2, 3
• Acute angle-closure glaucoma suspected (mid-dilated pupil, corneal edema, severe eye pain, very high IOP). 3
• Any acute vision loss with unclear etiology. 8, 4
• Uveitis or inflammatory eye disease (eye pain, photophobia, anterior chamber cells). 3

When to Refer to Neuro-Ophthalmology

• Unexplained optic atrophy requiring etiologic investigation. 2
• Atypical optic neuritis features. 5, 6
• Complex diplopia or cranial neuropathies not improving as expected. 1
• Papilledema requiring lumbar puncture and long-term management. 3

Common Pitfalls to Avoid

• Never dismiss transient monocular vision loss as "benign"—it carries significant stroke risk and requires urgent evaluation. 1
• Do not assume all third nerve palsies with pupil involvement are aneurysmal or all pupil-sparing are microvascular—atypical features require imaging. 1
• Do not delay GCA treatment waiting for biopsy results—permanent bilateral blindness can occur within days. 1
• Do not order only CT head for suspected neuro-ophthalmic pathology—MRI is far superior for optic nerve, chiasm, and posterior fossa evaluation. 3, 5, 7
• Do not assume normal visual acuity excludes serious pathology—patients with chiasmal compression or optic neuritis may have 20/20 vision initially. 5

Quality of Life Considerations

• Vision loss significantly impairs activities of daily living, driving privileges, reading ability, and is associated with worse cognition and mental health in older patients. 9
• Refer patients with permanent vision loss to low-vision occupational therapy and rehabilitation services. 2, 9
• Screen for and treat common comorbid ophthalmic conditions (dry eye, refractive error, cataracts) that worsen quality of life. 9
• Diplopia management: prisms, occlusion therapy, or botulinum toxin may improve function while awaiting spontaneous recovery or surgical intervention. 1